The proposed research is aimed at investigating the inhomogeneity of gas mixing and ventilation distribution in the lungs of normal subjects and patients with various types of airflow obstruction. The research will focus on the distinction between diffusion mechanisms within the lung periphery and diffusion independent ventilation mal-distribution among larger lung units. Single breath washouts of inert, soluble gases of different diffusivity, as well as a new analysis of the multiple breath washout will be utilized for this purpose. In addition, the mixing and axial dispersal of a soluble gas in the trachea will be examined. Theoretical mathematical models yielding numerical solutions of the gas transport equation will be applied to many of the questions addressed. A mathematical model of intra acinar gas mixing, incorporating geometrical asymmetry, will be extended to examine the effect of nonuniformity of intra acinar gas concentrations on gas exchange in the acinus as a whole. The analysis should help to clarify the influence of intra acinar blood flow distribution on gas exchange and the relationship of expired gas concentrations to "mean alveolar" concentrations. The effect on gas exchange of cardiogenic gas mixing will be examined in dogs by reversibly abolishing cardiogenic mixing by instillation of 50-100ml of saline into the peri-cardium. The research will also include a study of rib cage shape changes in normal subjects at rest, during moderate exercise, and during voluntary rapid breathing. Comparison with shape changes during rapid single breath inspirations should help to clarify and dynamic gas distribution during cyclic breathing and in single inspirations.